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Xenografts models of colorectal adenocarcinoma in nude mice: comparative analysis between implantation in cecum or in distal colon

Grant number: 10/17491-9
Support type:Scholarships abroad - Research
Effective date (Start): January 10, 2011
Effective date (End): March 01, 2011
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:Denise Gonçalves Priolli
Grantee:Denise Gonçalves Priolli
Host: Maria Filomena Rabaça Roque Botelho
Home Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil
Local de pesquisa : Universidade de Coimbra (UC), Portugal  

Abstract

Realistic models for colorectal cancer are necessary for study of cancer biology and assessment of therapeutic interventions. An animal model of colorectal cancer should ideally meet the biological characteristics and behaviors similar to human tumors, especially tumor location. Currently, the most accurate representation of orthotropic model of human colon cancer is through cecal inoculation. However, the cecum is an uncommon site of colorectal cancer is not ideal to mimic the microenvironment in which these tumors arise more frequently. Colorectal tumors are more incidents in the left-side of colon, especially in sigmoid and rectum. Nevertheless, few studies have used orthotropicmodel on the left side of the colon. This is due to early death of animals, because of this localization. Mice with implanted tumor on the left side of the colon die in a short period after tumor implantation due to colon obstruction. There are important differences between the left and right colon. Proximal and distal colons have distinct embryonic origins, which reflect in different anatomical aspects of each colon segment. Likewise, metabolic and physiological functions of each colon segment are also different. Recent genetic studies with microarray techniques have shown that genes expressions are different in the proximal and distal colon. Thus, it becomes important to establish whether the behavior of cells inoculated on the left or right colon produce identical or different tumors. This is necessary to extrapolation of found results as well to compare human tumors and human tumor implanted in animal model. The aim of this study is to present an animal model of colon adenocarcinoma on the left side suitable for studying the evolution with the implementation of cytotoxic therapy in vivo, comparing it to model implanted in cecum. Material and methods: Animals will be divided into two groups: those who underwent colostomy of the cecum (n = 10) and those subjected to descending colon diversion and distal mucous fistula (n = 10). Cultured cells of adenocarcinoma (WiDr) will be inoculated in the mucosa of the fistula and the cecum colostomy only after the return of bowel function. Images with 99mTc-MIBI will be made to identify the tumor after tumor implantation at 7, 15 and 21 days. After animal death, the study by conventional histopathology (HE) as well research of metastases in lymph nodes, liver and lung will done. Beta-catenin, p53 and MMP mutation will be studied by PCR. This study may provide a more accurate model of colorectal cancer with analysis of tumor progression and propagation, it will provide comparative analysis of effectiveness in metastasis development and allow in vivo therapeutic response measurement. (AU)